7ydh

Cryo EM structure of CD97/miniG13 complexCryo EM structure of CD97/miniG13 complex

Structural highlights

7ydh is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GNA13_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:15240885, PubMed:16705036, PubMed:16787920, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF1/p115RhoGEF, ARHGEF11/PDZ-RhoGEF and ARHGEF12/LARG) (PubMed:12515866, PubMed:15240885). GNA13-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway (PubMed:16705036, PubMed:16787920, PubMed:27084452). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (PubMed:11976333).[UniProtKB:P27601]^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

CD97 (ADGRE5) is an adhesion G protein-coupled receptor (aGPCR) which plays crucial roles in immune system and cancer. However, the mechanism of CD97 activation and the determinant of G(13) coupling selectivity remain unknown. Here, we present the cryo-electron microscopy structures of human CD97 in complex with G(13), G(q), and G(s). Our structures reveal the stalk peptide recognition mode of CD97, adding missing information of the current tethered-peptide activation model of aGPCRs. For instance, a revised "FXphiphiphi" motif and a framework of conserved aromatic residues in the ligand-binding pocket. Importantly, structural comparisons of G(13), G(q), and G(s) engagements of CD97 reveal key determinants of G(13) coupling selectivity, where a deep insertion of the alpha helix 5 and a closer contact with the transmembrane helix 6, 5, and 3 dictate coupling preferences. Taken together, our structural study of CD97 provides a framework for understanding CD97 signaling and the G(13) coupling selectivity.

Structural basis of CD97 activation and G-protein coupling.,Wang N, Qian Y, Xia R, Zhu X, Xiong Y, Zhang A, Guo C, He Y Cell Chem Biol. 2023 Nov 16;30(11):1343-1353.e5. doi: , 10.1016/j.chembiol.2023.08.003. Epub 2023 Sep 5. PMID:37673067^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Meigs TE, Fedor-Chaiken M, Kaplan DD, Brackenbury R, Casey PJ. Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin. J Biol Chem. 2002 Jul 5;277(27):24594-600. PMID:11976333 doi:10.1074/jbc.M201984200
↑ Suzuki N, Nakamura S, Mano H, Kozasa T. Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):733-8. PMID:12515866 doi:10.1073/pnas.0234057100
↑ Krakstad BF, Ardawatia VV, Aragay AM. A role for Galpha12/Galpha13 in p120ctn regulation. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10314-9. PMID:15240885 doi:10.1073/pnas.0401366101
↑ Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ. The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8173-8. PMID:16705036 doi:10.1073/pnas.0510254103
↑ Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ. A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem. 2006 Sep 8;281(36):26483-90. PMID:16787920 doi:10.1074/jbc.M604376200
↑ Yuan B, Cui J, Wang W, Deng K. Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis. Biochem Biophys Res Commun. 2016 May 13;473(4):1240-1246. PMID:27084452 doi:10.1016/j.bbrc.2016.04.048
↑ Wang N, Qian Y, Xia R, Zhu X, Xiong Y, Zhang A, Guo C, He Y. Structural basis of CD97 activation and G-protein coupling. Cell Chem Biol. 2023 Nov 16;30(11):1343-1353.e5. PMID:37673067 doi:10.1016/j.chembiol.2023.08.003

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Meigs TE, Fedor-Chaiken M, Kaplan DD, Brackenbury R, Casey PJ. Galpha12 and Galpha13 negatively regulate the adhesive functions of cadherin. J Biol Chem. 2002 Jul 5;277(27):24594-600. PMID:11976333 doi:10.1074/jbc.M201984200

[2] Suzuki N, Nakamura S, Mano H, Kozasa T. Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):733-8. PMID:12515866 doi:10.1073/pnas.0234057100

[3] Krakstad BF, Ardawatia VV, Aragay AM. A role for Galpha12/Galpha13 in p120ctn regulation. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10314-9. PMID:15240885 doi:10.1073/pnas.0401366101

[4] Kelly P, Moeller BJ, Juneja J, Booden MA, Der CJ, Daaka Y, Dewhirst MW, Fields TA, Casey PJ. The G12 family of heterotrimeric G proteins promotes breast cancer invasion and metastasis. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8173-8. PMID:16705036 doi:10.1073/pnas.0510254103

[5] Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ. A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem. 2006 Sep 8;281(36):26483-90. PMID:16787920 doi:10.1074/jbc.M604376200

[6] Yuan B, Cui J, Wang W, Deng K. Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis. Biochem Biophys Res Commun. 2016 May 13;473(4):1240-1246. PMID:27084452 doi:10.1016/j.bbrc.2016.04.048

[7] Wang N, Qian Y, Xia R, Zhu X, Xiong Y, Zhang A, Guo C, He Y. Structural basis of CD97 activation and G-protein coupling. Cell Chem Biol. 2023 Nov 16;30(11):1343-1353.e5. PMID:37673067 doi:10.1016/j.chembiol.2023.08.003

[1]

[2]

[3]

[4]

[5]

[6]

[7]